FDA approves new treatment for large brain aneurysms

The U.S. Food and Drug Administration has approved the cPAX Aneurysm Treatment System for surgery on brain aneurysms that are difficult to manage because of their size and shape.

An aneurysm is a bulge in the wall of a blood vessel, which can rupture as it increases in size, causing hemorrhage or death. Brain aneurysms often produce no symptoms until they grow and press on nerves in the brain, or until they begin to leak blood or rupture.

Aneurysms can be repaired in two ways: surgeons can close the base of the aneurysm with a surgical clip, or use a technique commonly known as coiling, in which surgeons use a catheter to thread metallic coils through a blood vessel in the groin and into the blood vessel in the brain that contains the aneurysm. Surgeons then fill the aneurysm with the detachable coils, which block it from circulation and cause blood to clot, effectively destroying the aneurysm.

Aneurysms larger than 10millimeters are difficult to treat with clipping or coiling. The cPAX Aneurysm Treatment System is indicated for use in those brain aneurysms.

“Like coiling, the cPAX Aneurysm Treatment System is a form of endovascular repair,” said Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health. “But instead of tiny metallic coils, it uses a special polymer material to fill the space within the aneurysm.”

The cPAX polymeric filler material can be secured in the aneurysm in one of two ways, either by insertion through openings in a permanent stent, which is a tiny metal scaffold placed along the vessel wall, or by using a temporary balloon catheter to block off the opening to the aneurysm and keep the filler material from coming out of the aneurysm as it is being delivered.

By filling the bulging space within the aneurysm with implant material, the blood flow through the aneurysm is stopped and any remaining space around the implant material clots. When filled with implant material and blood clot, and the risk of rupture of the aneurysm decreases.

The cPAX Aneurysm Treatment System was approved on April 1, 2011, under a Humanitarian Device Exemption (HDE). The HDE makes medical devices available to patients with rare medical conditions that affect fewer than 4,000 people a year. The approval for this HDE was based on safety data from two studies of 43 subjects.

The cPAX device system is indicated for use in adults ages 22 and older and should not be used in patients with an active infection or in those in whom anticoagulation and antiplatelet therapy is contraindicated.

The cPAX Aneurysm Treatment System is manufactured by Neurovasx Inc., Maple Grove, Min.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

Mayo Clinic Finds Seizure Generation in Brain is Isolated from Surrounding Brain Regions

Mayo Clinic researchers found that the part of the brain generating seizures in individuals with epilepsy is functionally isolated from surrounding brain regions. The researchers hope this finding could be a clinical biomarker to help identify individuals with abnormal brain function. This study was presented at the American Epilepsy Society's annual meeting in San Antonio on Dec. 4.

Epilepsy is a disorder characterized by the occurrence of two or more seizures. It affects almost 3 million Americans.

"The synchronization of local and distributed neuronal assemblies underlies fundamental brain processes like perception, learning and cognition," says Gregory Worrell, M.D., Ph.D., a Mayo Clinic epileptologist and an author of this study. "In neurological disease, neuronal synchrony can be altered, and in epilepsy the synchrony plays an important role in the generation of seizures."

Mayo Clinic researchers investigated neuronal synchrony by studying intracranial EEG (electroencephalogram) recordings from patients with epilepsy and control subjects with facial pain. Researchers discovered that the control patients had greater average synchrony than patients with focal epilepsy (when seizures are produced in a small part of the brain, not the entire brain). When implanted electrode pairs bridged seizure-generating brain and other brain regions, the synchrony was significantly less than between other electrode pairs in the epileptic brain and the control brain. The team also found that with greater activity in the seizure-generating region, there was less synchrony with neighboring tissue outside that region.

"Our study shows us that the part of the brain generating seizures is isolated from the surrounding brain regions," says Dr. Worrell. "This finding could serve as a clinical biomarker of an abnormal brain, and it can also be useful in epilepsy surgery and brain stimulation treatments, as well as helping us understand how seizures are generated." Other scientists involved in this research include C. Warren, Ph.D.; S. Hu; S. Stead, M.D., Ph.D.; B. Brinkmann, and M. Bower, Ph.
---
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
Facebook: http://facebook.com/ArtsAcrossGA
www.FayetteFrontPage.com
Twitter: @FayetteFP

GSU researchers explore how pain in infancy can change pain sensitivity in adulthood

Scientists at Georgia State University have uncovered the mechanisms of how pain in infancy alters how the brain processes pain in adulthood.

Research is now indicating that infants who spent time in the neonatal intensive care unit (NICU) show altered pain sensitivity in adolescence. These results have profound implications and highlight the need for pre-emptive and post-operative pain medicine for newborn infants.

The study, published online in the journal Frontiers in Behavioral Neuroscience, sheds light on how the mechanisms of pain are altered after infant injury in a region of the brain called the periaqueductal gray, which is involved in the perception of pain.

Using Sprague-Dawley rats, Jamie LaPrairie, a graduate student in associate professor Anne Murphy’s laboratory, examined why the brief experience of pain at the time of birth permanently decreased pain sensitivity in adulthood.

Endogenous opioid peptides, such as beta-endorphin and enkephalin, function to inhibit pain. They’re also the ‘feel good’ substances that are released following high levels of exercise or love. Since these peptides are released following injury and act like morphine to dampen the experience of pain, LaPrairie and Murphy tested to see if the rats, who were injured at birth, had unusually high levels of endogenous opioids in adulthood.

To test this hypothesis, LaPrairie and Murphy gave adult animals that were injured at the time of birth a drug called naloxone. This drug blocks the actions of endogenous opioids. After animals received an injection of naloxone, they behaved just like an uninjured animal.

The scientists then focused on the periaqueductal gray region to see if inflammation at birth altered the natural opioid protein expression in this brain region. Using a variety of anatomical techniques, the investigators showed that animals that were injured at birth had endogenous opioid levels that were two times higher than normal.

While it’s beneficial to decrease pain sensitivity in some cases, it’s not good to be completely resilient to pain.

“Pain is a warning sign that something is wrong,” Murphy explained. “For example, if your hand is in water that's too hot, pain warns you to remove it before tissue damage occurs.”

Interestingly, while there is an increase in endorphin and enkephalin proteins in adults, there is also a big decrease in the availability of mu and delta opioid receptors. These receptors are necessary in order for pain medications, such as morphine, to work. This means that it takes more pain-relieving medications in order to provide relief as there are fewer available receptors in the brain. Studies in humans are reporting the same phenomenon.

The number of invasive procedures an infant experienced in the NICU is negatively correlated with how responsive the child is to morphine later in life; the more painful procedures an infant experienced, the less effective morphine is in alleviating pain.

The study by LaPrairie and Murphy has major implications for the treatment of infants in neonatal intensive care. On average, a prematurely born infant in a neonatal intensive care unit will experience 14 to 21 invasive procedures a day, including heel lance, insertion of intravenous lines, and intubation. All of these procedures are quite painful and are routinely conducted without prior analgesics or anesthetics.

“It’s imperative that pain be treated,” Murphy said. “We once assumed that a newborn infant is insensitive to pain, and this is clearly not the case. Even at that period of time, the central nervous system is able to respond to pain, and our studies show that the experience of pain completely changes the wiring of the brain in adulthood.”

The next steps in Murphy’s research include the study of how neonatal injury at birth alters stress responses, as well as the affects of infant injury on long-term learning and memory.

LaPrairie’s and Murphy’s work was supported by the National Institutes of Health, the Center for Behavioral neuroscience, a consortium of seven universities at Georgia State, and the Georgia State Brains and Behavior Program.

The article, titled “Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal gray,” appears in the September 2009 edition of journal Frontiers in Behavioral Neuroscience, Vol. 3, p. 1-11.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Risky Behavior in Adolescents May Signal Mature Brain

A new study using brain imaging to study teen behavior indicates that adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

The brain goes through a course of maturation during adolescence and does not reach its adult form until the mid-twenties. A long-standing theory of adolescent behavior has assumed that this delayed brain maturation is the cause of impulsive and dangerous decisions in adolescence. The new study, using a new form of brain imaging, calls into question this theory.

In order to better understand the relationship between high risk-taking and the brain’s development, Emory University and Emory School of Medicine neuroscientists used a form of magnetic resonance imaging (MRI) called diffusion tensor imaging (DTI) to measure structural changes in white matter in the brain. The study’s findings are published in the Aug. 26, 2009 PLoS ONE.

“In the past, studies have focused on the pattern of gray matter density from childhood to early adulthood, says Gregory Berns, MD, PhD, principal investigator and professor of Psychiatry and Neuroeconomics at Emory University and director of the Center for Neuropolicy. “With new technology, we were able to develop the first study looking at how development of white matter relates to activities in the real world.”

Gray matter is the part of the brain made up of neurons, while white matter connects neurons to each other. As the brain matures, white matter becomes denser and more organized. Gray matter and white matter follow different trajectories. Both are important for understanding brain function.

The study enrolled 91adolescents ages 12 through 18 over a three-year period. Levels of engagement in dangerous behaviors were measured by a survey that included questions about the teens’ thrill seeking behaviors, reckless behaviors, rebellious behaviors and antisocial behaviors. DTI was used to measure corresponding structural changes in white matter.

“We were surprised to discover that risk-taking was associated with more highly-developed white matter – a more mature brain,” says Berns. “We were also surprised to learn that except for slightly higher scores in risk-taking, there was no significant difference in the maturity of the white matter between males and females.”

Berns suggests that doing adult-like activities requires sophisticated skills.

“Society is a lot different now than it was 100 years ago when teens were expected to go to work and raise a family,” says Berns. “Now, adolescents aren’t expected to act like adults until they are in their twenties, when they have finished their education and found a career.

“You could make the case that in this country, biological capacity shows up long before the wisdom that comes with time is fully developed,” notes Berns.

Berns says more studies need to be done to determine if early brain development predisposes someone to engage in risky behaviors, or if the risky behavior drives the maturation of the brain.

The CDC reports that, 27,000 people between the ages of 10 and 24 die from bad decisions in the United States per year. Additionally, it has been shown that the period of mid-adolescence (ages 15 through 19) is the time when teens are more likely to begin high-risk behaviors such as drinking, abusing drugs or driving recklessly.

Other researchers who contributed to this study include, Sara Moore, BS, Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine and C. Monica Capra, PhD, the Department of Economics and the Center for Neuropolicy, Emory University.

This study was funded by grants from the National Institute on Drug Abuse.

“Adolescent Engagement in Dangerous Behaviors Is Associated with Increased White Matter Maturing of Frontal Cortex”, PLoS ONE, 8/26/09, 10.1371
---
Community News You Can Use
Follow us on Twitter: @gafrontpage
www.FayetteFrontPage.com
www.GeorgiaFrontPage.com
www.PoliticalPotluck.com
www.ArtsAcrossGeorgia.com
---

Avian Influenza Strain Primes Brain for Parkinson's Disease

/PRNewswire/ -- At least one strain of the H5N1 avian influenza virus leaves survivors at significantly increased risk for Parkinson's disease and possibly other neurological problems later in life, according to new research from St. Jude Children's Research Hospital.

In the August 10 online early edition of the Proceedings of the National Academy of Sciences, researchers reported that mice which survived infection with an H5N1 flu strain were more likely than uninfected mice to develop brain changes associated with neurological disorders like Parkinson's and Alzheimer's diseases. Parkinson's and Alzheimer's involve loss of brain cells crucial to a variety of tasks, including movement, memory and intellectual functioning. The study revealed the H5N1 flu strain caused a 17 percent loss of the same neurons lost in Parkinson's as well as accumulation in certain brain cells of a protein implicated in both diseases.

"This avian flu strain does not directly cause Parkinson's disease, but it does make you more susceptible," said Richard Smeyne, Ph.D., associate member in St. Jude Developmental Neurobiology. Smeyne is the paper's senior author.

"Around age 40, people start to get a decline in brain cells. Most people die before they lose enough neurons to get Parkinson's. But we believe this H5N1 infection changes the curve. It makes the brain more sensitive to another hit, possibly involving other environmental toxins," Smeyne explained.

Smeyne noted the work involved a single strain of the H5N1 flu virus, the A/Vietnam/1203/04 strain. The threat posed by other viruses, including the current H1N1 pandemic flu virus, is still being studied.

Early indications are that the H1N1 pandemic strain carries a low neurologic risk, said Richard Webby, Ph.D., director of the World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds, which is based at St. Jude. Webby, who is also an associate member of the St. Jude Department of Infectious Diseases, was not involved in the H5N1 study led by Smeyne.

This study also supports the theory that a hit-and-run mechanism is at work in Parkinson's disease. The investigators believe the H5N1 infection sparks an immune response that persists long after the initial threat is gone, setting patients up for further devastating losses from a second hit, possibly from another infection, drug or environmental toxin. In this case, researchers believe the flu virus is the first hit that sets up development of Parkinson's at a later time.

An estimated 4.1 million Americans, including 1 to 2 percent age 55 and older, have Parkinson's. Many suspect both genetic and environmental factors play a role in its development. The disease is linked to the death of dopamine-secreting cells in an area of the midbrain known as the substantia nigra pars compacta (SNpc). Dopamine is a neurotransmitter responsible for stimulating the motor neurons that control movement. Parkinson's is usually diagnosed after individuals lose 70 to 80 percent of the dopamine-producing cells. Treatment is available, but there is no cure.

Flu is primarily a respiratory disease, but indirect evidence dating back to 1385 links it to neurological problems, including the brain inflammation known as encephalitis. The association between flu and brain disorders like Parkinson's was strengthened by an outbreak of encephalitic lethargic, also known as von Economo's encephalopathy, following the 1918 Spanish flu pandemic. Some of those patients developed Parkinson's symptoms.

St. Jude researchers launched this study nearly three years ago in response to the threat posed by avian flu. Smeyne said there was concern about possible long-term neurological risks facing H5N1 survivors.

Previous studies had isolated H5N1 in the nervous system. But this is the first to show the path the virus takes to enter the brain as well as the aftermath of the infection. Smeyne said the virus' path from the stomach through the nervous system and into the brain is reminiscent of how Parkinson's unfolds.

In this study, mice were infected with an H5N1 flu strain isolated in 2004 from a patient in Vietnam. Robert Webster, Ph.D., said the strain remains the most virulent of the avian flu viruses. Webster, a co-author of the study, holds the Rose Marie Thomas Chair in Infectious Diseases at St. Jude.

About two-thirds of the mice developed flu symptoms, primarily weight loss. After three weeks there was no evidence of H5N1 in the nervous systems of the mice that survived.

But the inflammation the infection triggered within the brain continued for months. It was similar to inflammation associated with inherited forms of Parkinson's. Although the tremor and movement problems disappeared as flu symptoms eased, investigators reported that 60 days later mice had lost roughly 17 percent of dopamine-producing cells in SNpc, a structure found in the midbrain.

Researchers also found evidence that the avian flu infection led to over-production of a protein found in the brain cells of individuals with both Alzheimer's and Parkinson's diseases. The protein, alpha-synuclein, collected in H5N1-infected cells throughout the brain, including the midbrain where key dopamine-producing cells are located. There was little protein accumulation in the brain cells of uninfected mice.

The study marks the first time scientists were able to naturally trigger the protein build-up in an experimental Parkinson's system. "The virus activates this protein," Smeyne explained.

Other authors in this paper include Haeman Jang, David Boltz and Yun Jiao (St. Jude); and Katharine Sturm-Ramirez and Kennie Shephard (formerly of St. Jude).

This work was supported in part by the National Institute of Allergy and Infectious Diseases, National Parkinson's Foundation, Michael J. Fox Foundation, National Institutes of Health and ALSAC.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page
www.artsacrossgeorgia.com
Arts Across Georgia

Clot-Buster Boosts Survival, Decreases Disability for Deadly Subset of Stroke

New results from a multicenter study led by Johns Hopkins show that patients who got an experimental clot-busting treatment for a particularly lethal form of stroke were not only dramatically more likely to survive but also continued to shed lingering disabilities six months later. The findings, announced at the International Stroke Conference in San Diego on Feb. 19, are likely to build support for the use of tissue plasminogen activator (tPA) in patients with intracranial hemorrhage, a treatment-resistant form of stroke marked by brain bleeding.

Last May, study leader Daniel Hanley, M.D., professor of neurology at the Johns Hopkins School of Medicine, and his colleagues reported early findings among 52 intracranial hemorrhage (ICH) patients treated with tPA given by catheter directly into patients' brains to bathe and destroy blood clots with this clot-busting agent. The researchers worked with patients at 38 study sites scattered throughout the United States, as well as in Canada, Germany and Finland.

The treatment, developed by Hanley's team, gives low doses of tPA over several days after strokes involving intracranial hemorrhage.

This drug normally isn't recommended for conditions that involve bleeding, such as ICH, because it can increase the risk of further hemorrhage. However, since tPA is effective at breaking up clots in other conditions, such as heart attacks and other types of strokes, Hanley and his colleagues have been studying its safety and efficacy for treating ICH.

Early results from this study using information collected 30 days after tPA treatment showed that about 80 percent survived, compared to data from previous studies showing that about 80 percent of untreated ICH patients die. In the new study, the researchers report on the patients' progress six months after treatment using assessments for overall levels of disability as well as their skill in accomplishing specific tasks often affected by stroke, such as dressing, bathing or walking.

The researchers found that about 10 percent of patients had no lingering disability after six months. Another 40 percent had only mild to moderate disability and were independently caring for themselves at home by 180 days, but required assistance with everyday tasks such as lifting heavy objects. Even patients who were initially more severely disabled continued to improve months after treatment, with the majority scoring lower on disability assessments after six months compared to the same assessments taken at 30 days.

"We're painting a pretty good picture for quality of life after our treatment for ICH," Hanley says. "Survival doesn't have to mean just getting by-we're showing that it can mean truly living again."

Hanley adds that patients, families, physicians and ethicists worry deeply about the impact of stroke treatments that keep patients alive but leave them with a sharply curbed quality of life. "Our new treatment appears to greatly increase patients' chances for survival and quality of life similar to what they experienced before they had their stroke," he says.

Intracerebral hemorrhage, or ICH, causes blood to pool and clot inside the brain's interior cavities, building up pressure within the brain. The higher pressure, along with inflammation caused by chemicals in the trapped blood, can irreversibly damage the brain, usually leading to death or extreme disability.

Hanley and colleagues, with a clinical planning grant from the National Institute of Neurological Diseases and Stroke will design a pivotal test to assess the value of tPA therapy on a much larger group of ICH patients. They expect to start this clinical trial imminently..

Other Johns Hopkins researchers who participated in this study include Wendy Ziai, M.D.; Ricardo Carhuapoma, M.D.; Neal Naff, M.D.; Becky Sullivan, M.B.A.; Timothy Morgan, B.S.; Eric Melnychuk, B.A., E.M.T.-B; Susan Rice, R.N., M.P.H., C.C.R.P.; Amber Stahl, B.A.; Shannon LeDroux, B.S.; Amanda Bistran, B.S.; and Karen Lane, C.M.A., C.C.R.P.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Do You Know You're Having a Stroke?

/PRNewswire-USNewswire/ -- A Mayo Clinic study shows a majority of stroke patients don't think they're having a stroke -- and as a result -- delay seeking treatment until their condition worsens. The findings appear in the current issue of Emergency Medicine Journal at http://emj.bmj.com/.

Researchers studied 400 patients who were diagnosed at Mayo Clinic's emergency department with either acute ischemic stroke or a transient ischemic attack (TIA), a temporary interruption of blood flow to part of the brain.

Less than half of the patients -- 42 percent -- thought they were having a stroke. In fact, most in the study did not go to the emergency room when symptoms appeared. The median time from onset of symptoms to arrival at the hospital was over three and a half hours. Most said they thought the symptoms would simply go away. The delay in seeking medical help was the same among men and women.

When asked how they knew about stroke symptoms, nearly one-fifth said they thought a stroke always came on gradually. Just over half (51.9 percent) said they thought that seeking medical care immediately was important.

Significance of the findings

"Time is crucial in treating stroke," says Latha Stead, M.D., emergency medicine specialist and lead author of the study. "Each individual's medical background differs and affects recovery, but in general the sooner a patient experiencing a stroke reaches emergency care, the more likely the stroke can be limited and the condition managed to prevent further damage and improve recovery." The researchers say their findings clearly indicate that better public understanding of stroke symptoms will lead to a faster response and better outcomes.

What you should know

Strokes can happen quickly or can occur over several hours, with the condition continually worsening. The thrombus or clot that is causing the stroke can frequently be dissolved or disintegrated so blood can again flow to the brain. In such cases, immediate treatment can mean the difference between a slight injury and a major disability. Interestingly only 20.8 percent of the participants knew about such treatment. By use of stents, medications and other technology, physicians can stop a stroke from spreading and greatly limit damage. Stroke symptoms include:

* Sudden numbness, weakness, or paralysis of your face, arm or leg -- usually on one side of the body

* Sudden difficulty speaking or understanding speech (aphasia)
* Sudden blurred, double or decreased vision
* Sudden dizziness, loss of balance or loss of coordination

* A sudden, severe "bolt out of the blue" headache or an unusual headache, which may be accompanied by a stiff neck, facial pain, pain between your eyes, vomiting or altered consciousness

* Confusion or problems with memory, spatial orientation or perception

In such cases, a stroke gives no warning. But one possible sign of an impending stroke is a TIA. The signs and symptoms of TIA are the same as for a stroke, but they last for a shorter period -- several minutes to a few hours -- and then disappear, without leaving apparent permanent effects. You may have more than one TIA, and the signs and symptoms may be similar or different. A TIA indicates a serious risk that a full-blown stroke may follow.

Other Mayo researchers involved in the study were Lekshmi Vaidyanathan, M.B.B.S.; Maria Bellolio, M.D.; Rahul Kashyap, M.B.B.S.; Anjali Bhagra, M.B.B.S.; Rachel Gilmore, M.B.B.Ch.; Wyatt Decker, M.D.; Sailaja Enduri, M.B.B.S.; Shaily Mishra, Ph.D.; Helen Wood, R.N.; Ayman Yassa, M.D.; Ann Hoff, M.D.; and Robert Brown, M.D. Dr. Stead is supported by the Mayo Emergency Medicine Research Career Development Award and Mayo Clinic.

-----
www.fayettefrontpage.com
Fayette Front Page
Community News You Can Use
Fayetteville, Peachtree City, Tyrone
www.georgiafrontpage.com
Georgia Front Page

Alzheimer's Gene Slows Brain's Ability to Export Toxic Protein

PRNewswire-USNewswire/ -- The only known genetic risk factor for Alzheimer's disease slows down the brain's ability to export a toxic protein known as amyloid-beta that is central to the damage the disease causes, scientists have found.

The research, published Nov. 13 by the Journal of Clinical Investigation, provides new clues into the workings of a protein known as apolipoprotein E4, or ApoE4. People who carry two copies of the gene have roughly eight to 10 times the risk of getting Alzheimer's disease than people who do not.

The new results mark a step toward resolving a longstanding question that scientists have had about exactly how ApoE4 increases a person's risk for the disease. The findings point to differences in the way that amyloid-beta is removed from the brain depending on which ApoE protein is involved.

Scientists found that when ApoE4 is present, the brain is less efficient at ridding itself of the toxic material, because a molecule that is much slower at removing the substance becomes much more involved.

The new results are in line with a body of research amassed over the last 15 years by the leader of the team, Berislav Zlokovic, M.D., Ph.D., of the University of Rochester Medical Center, that blood circulation plays a key role in the disease. His team has identified much of the molecular machinery that allows amyloid-beta to sidestep the body's safeguards and enter the brain, and he has discovered molecules that falter when the toxic protein accumulates in the brain.

"Our latest findings help explain one of the major risk factors for Alzheimer's disease," said Zlokovic. "ApoE4 changes the brain's ability to rid itself of amyloid-beta. It's becoming more and more apparent that the brain's ability to clear out amyloid-beta, through the vascular system and across the blood-brain barrier, is central to the development of Alzheimer's disease."

In the latest work the Rochester team, working with colleagues at Washington University School of Medicine in St. Louis, found that a molecule known as very low-density lipoprotein receptor, or VLDLR, is an active - but slow - player in the removal of amyloid-beta from the brain. That step is crucial: Once amyloid-beta gets out of the brain and into the body, it can be eliminated easily.

"It's as if you have a pile of trash building up in the brain, and you need to move the trash away before it becomes toxic," said Rashid Deane, Ph.D., one of the authors of the paper and research professor of Neurosurgery at the University of Rochester Medical Center.

"We've known that the brain uses a molecule called LRP1, which is extremely efficient and acts like a fast ferry to remove amyloid-beta. Now we've found that there is another molecule involved, which works much more slowly, and it's especially active when amyloid is coupled to ApoE4," Deane added.

The team showed that speedy LRP1 is central to removing amyloid-beta when ApoE2 or ApoE3 is involved, with the slower VLDLR picking up some of the slack. But when the form of the gene that puts people at risk, ApoE4, is involved, VLDLR nearly alone is responsible for hauling the amyloid-beta away.

"It's like having a choice between a fast ferry and a slow ferry," said Deane. "For reasons we don't yet understand, when ApoE4 is involved, the slow ferry is used almost exclusively. This means that the amyloid-beta isn't removed as quickly as it otherwise would, potentially giving it a chance to accumulate, like we see in the brains of patients with Alzheimer's disease."

The team found that LRP1 is able to export amyloid from the brain about 20 times faster than VLDLR. Consequently, in mice with the more efficient versions of the ApoE protein, ApoE2 and ApoE3, amyloid is cleared out of the brain at a rate about twice or three times as fast as it is in mice with the ApoE4 protein. Amyloid deposits accumulate in the brains of mice with the ApoE4 protein in much higher amounts, about 10 to 15 times as much as in the brains of mice with either ApoE2 or ApoE3.

Not only do the ApoE proteins help determine how quickly amyloid-beta is removed from the brain; the proteins actually couple with amyloid-beta in the brain to form sticky complexes. This gunk gathers around cells and is much more difficult to remove from the brain than free-floating amyloid-beta. Companies are trying to develop drugs that would break up the relationship, freeing amyloid-beta and making it easier to remove from the brain.

The work described in the paper published in the Journal of Clinical Investigation was funded by a Senator Jacob Javits Award from the National Institute of Neurological Disorders and Stroke, and by the National Institute on Aging.

In addition to Zlokovic and Deane, other Rochester authors of the paper include instructor Abhay Sagare, Ph.D., who performed much of the research; technicians Katie Hamm, Margaret Parisi, and Steven Lane; and neuroscientist David Holtzman and graduate student Mary Beth Finn at Washington University School of Medicine.

Zlokovic is a founder of a company, Socratech, which is seeking to commercialize his team's discoveries about how amyloid-beta collects in the brain and how it might be removed more efficiently. He is also the Dean's Professor of Neurosurgery and Neurology and director of the Center for Neurodegenerative and Vascular Brain Disorders.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Mouse Studies Suggest Daily Dose of Ginkgo may Prevent Brain Cell Damage After a Stroke

Working with genetically engineered mice, researchers at Johns Hopkins have shown that daily doses of a standardized extract from the leaves of the ginkgo tree can prevent or reduce brain damage after an induced stroke.

The scientists, in a report published in Stroke, say their work lends support to other evidence that ginkgo biloba triggers a cascade of events that neutralizes free radicals known to cause cell death.

"It's still a large leap from rodent brains to human brains but these results strongly suggest that further research into the protective effects of ginkgo is warranted," says lead researcher Sylvain Doré, Ph.D., an associate professor in the Department of Anesthesiology and Critical Care Medicine. "If further work confirms what we've seen, we could theoretically recommend a daily regimen of ginkgo to people at high risk of stroke as a preventive measure against brain damage."

In the study, researchers gave ginkgo biloba EGb 761 - a lab-quality form of the extract - to normal mice and HO-1 knockout mice, mice lacking the gene that produces the enzyme heme oxygenase-1(HO-1). HO-1 breaks down heme, a common iron molecule found in blood, into carbon monoxide, iron and biliverdin. HO-1 has been shown to act as an antioxidant and have a protective effect against inflammation in animal models.

Doré and his team gave 100 milligrams per kilogram of EGb 761 extract orally once daily for seven days before inducing stroke in the mice by briefly blocking an artery to one side of the brain.

After stroke induction, the mice were tested for brain function and brain damage. One such test, for example, involves running patterns, another tests reaction to an external stimulus. Similar tests were conducted on mice that did not receive the ginkgo extract.

Neurobehavioral function was evaluated before the study and at 1, 2 and 22 hours after stroke using a four-point scale: (1) no deficit, (2) forelimb weakness, (3) inability to bear weight on the affected side, (4) no spontaneous motor activity.

Results showed that normal mice that were pretreated had 50.9 percent less neurological dysfunction and 48.2 percent smaller areas of brain damage than untreated mice. These positive effects did not exist in the HO-1 knockout mice.

"Our results suggest that some element or elements in ginkgo actually protect brain cells during stroke," says Doré.

Roughly 700,000 people experience a stroke in the United States annually. Of those, 87 percent have an ischemic stroke, which is caused by a blocked artery in the brain. Some brain damage occurs simply from the lack of blood getting to brain cells; however, it is known that an increase in the presence of free radicals at the site of an ischemic stroke - once the clot is cleared and the blood supply returns - is also a major cause of resulting brain cell damage. Free radicals are toxic oxygen molecules that are produced when cells die. According to Doré and his team, ginkgo increases HO-1 levels, and the antioxidant properties of this enzyme eliminate free radicals at the surrounding regions of the stroke site.

The only current treatment for ischemic stroke is to clear the clot with tissue plasminogen activator (tPA) or other means. This, however, offers no real protection against the cell damage that occurs when blood flow is restored.

"Ginkgo has long been touted for its positive effects on the brain and is even prescribed in Europe and Asia for memory loss," says Doré. "Now we have a possible understanding for how ginkgo actually works to protect neurons from damage."

Native to China, the ginkgo tree is grown as an ornamental shade tree in Australia, Southeast Asia, Europe, Japan and North America. It is commercially cultivated in France and the United States. It has a grey bark, reaches a height of 35 meters and a diameter of 3 to 4 meters. It has deciduous, fan-like leaves that are green, grey-yellow, brown or blackish.

Additional researchers include Sofiyan Saleem, Ph.D., and Hean Zhuang, M.D., of the Department of Anesthesiology and Critical Care Medicine, and Shyam Biswal, Ph.D., of the Department of Environmental Health Sciences, all from Johns Hopkins.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

Zen Training Speeds the Mind's Return After Distraction, Brain Scans Reveal

Experienced Zen meditators can clear their minds of distractions more quickly than novices, according to a new brain imaging study.

After being interrupted by a word-recognition task, experienced meditators’ brains returned faster to their pre-interruption condition, researchers at Emory University School of Medicine found.

The results are published online by the journal Public Library of Science One (PLoS ONE). Read the results.

Giuseppe Pagnoni, PhD, Emory assistant professor of psychiatry and behavioral sciences, and co-workers used functional magnetic resonance imaging (fMRI) to examine changes in blood flow in the brain when people meditating were interrupted by stimuli designed to mimic the appearance of spontaneous thoughts.

The study compared 12 people from the Atlanta area with more than three years of daily practice in Zen meditation with 12 others who had never practiced meditation.

While having their brains scanned, the subjects were asked to focus on their breathing. Every once in a while, they had to distinguish a real word from a nonsense word presented at random intervals on a computer screen and, having done that, promptly “let go” of the just processed stimulus by refocusing on their breath.

The authors found that differences in brain activity between experienced meditators and novices after interruption could be seen in a set of areas often referred to as the "default mode network." Previous studies have linked the default mode network with the occurrence of spontaneous thoughts and mind wandering during wakeful rest.

After interruption, experienced meditators were able to bring activity in most regions of the default network back to baseline faster than non-meditators. This effect was especially prominent in the angular gyrus, a region important for processing language.

"This suggests that the regular practice of meditation may enhance the capacity to limit the influence of distracting thoughts. This skill could be important in conditions such as attention deficit and hyperactivity disorder, obsessive-compulsive disorder, anxiety disorder and major depression, characterized by excessive rumination or an abnormal production of task-unrelated thoughts," Pagnoni says.

Dr. Pagnoni recently moved from Emory to the University of Modena and Reggio Emilia in Italy.

The research was funded by a National Institutes of Health grant to the Emory Center for Research on Complementary and Alternative Medicine in Neurodegenerative Diseases.

Reference:
Pagnoni et al, PLoS One, Volume 3, Issue 9 (September 2008) “Thinking about Not-Thinking”: Neural Correlates of Conceptual Processing during Zen Meditation.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

News to Use in Fayetteville, Newnan, Atlanta, Peachtree City and all of Georgia

Vaccine May Double Survival in Patients with Deadly Brain Tumors

A vaccine aimed at inducing immunity to the most common and deadly type of brain tumor may stave off recurrence and more than double survival in patients, according to a new study led by researchers in Duke's Preston Robert Tisch Brain Tumor Center.

"This vaccine represents a very promising therapy for a cancer that comes out of the blue and robs people of something most of us take for granted -- time," said John Sampson, M.D., Ph.D., a neurosurgeon at Duke and lead investigator on this study. "The possibility of doubling expected survival -- with few if any side effects -- would represent a big step and a lot of hope for this group of patients."

Sampson presented the results of this Phase II study during an oral presentation at the annual American Society of Clinical Oncology meeting in Chicago on June 2, 2008. The study was funded by the National Institutes of Health and Celldex Therapeutics, a subsidiary of Avant Immunotherapeutics, which has licensed the rights to the vaccine and provided vaccine for use in the study.

The vaccine targets a protein expressed on about half of all glioblastoma multiforme (GBM) tumors. The protein, known as epithelial growth factor receptor variant III (EGFRvIII), is not expressed in normal tissues but is prevalent in GBMs, which makes it an attractive target for a vaccine, Sampson said.

The vaccine targets the protein and enhances immune response to it, killing tumor cells that express the protein and preventing the re-growth of brain tumors in patients who have already been diagnosed and treated with standard regimens including surgery, chemotherapy and radiation.

This study included 23 patients, treated at Duke and at M.D. Anderson Cancer Center. Patients had all been diagnosed with GBMs, and had been treated with standard therapy. Patients in the trial received vaccine injections monthly and were given a chemotherapeutic agent called temozolomide in conjunction with the vaccine treatments. The temozolomide is thought to enhance the immune response to the EGFRvIII, Sampson said.

"This reflected something of a surprising conclusion, because it stands to reason that chemotherapy, which suppresses the body's immune system, would make the vaccine less effective," Sampson said. "What we found was that the opposite is true. While the body is recovering from chemotherapy, immune response is actually stronger as the immune system overcompensates in order to right itself. It's the perfect time to introduce a vaccine."

Patients in the study survived without re-growth of their tumors for a median of 16.6 months, which more than doubles the usual 6.4-month expected progression-free survival in these patients.

Study patients lived for an average of 33.1 months; patients who are diagnosed with GBMs and treated with standard therapy typically live an average of 14.3 months.

"We're more than doubling survival time in this group, and we have some patients who are four, five or six years out from diagnosis, which is virtually unheard of in these people," Sampson said.

The vaccine has caused virtually no side effects; swelling at the injection site is often a patient's only complaint. A Phase III trial is now open at more than 20 sites nationwide.

Other researchers involved with this study include Gary Archer, Darell Bigner, Henry Friedman, Duane Mitchell and David Reardon of Duke; Amy Heimberger and Raymond Sawaya of M.D. Anderson Cancer Center; and Tom Davis and Tibor Keler of Celldex Therapeutics.

Brain Tumor Foundation for Children Supports Emory Study of Deadly Tumor Types

The Brain Tumor Foundation for Children has awarded Emory University scientist Erwin G. Van Meir, PhD, a $50,000 grant for pre-clinical research on two of the deadliest forms of pediatric brain tumors--gliomas and medulloblastomas.

"We are very grateful for the foundation support and all the dedicated individuals who helped raise these funds. Such efforts make a big difference," says Van Meir.

Van Meir will study a novel small molecule that may inhibit the role of a key protein, hypoxia-inducible factor (HIF-1). HIF-1 is linked to the malignant progression of tumors found in the central nervous system (CNS) and activates angiogenesis, the process that initiates the formation of new blood vessel needed for tumor growth.

"This is a very exciting opportunity," says Van Meir. "Using mouse models, we will be able to test for the first time a novel small chemical molecule as a candidate drug to treat the two most lethal forms of childhood cancer. We evidenced the anti-cancer action of this novel molecule discovered in our laboratory in 2006, and now we will be able to test whether its action extends to pediatric brain tumors. This study provides new hope for children with brain tumors who urgently need new treatments."

Brain tumors are the second-leading cause of cancer deaths in children younger than 15 and the most common type of childhood cancer. Each year, roughly 2,000 children are diagnosed with brain tumors. Treatment may include surgery, radiation therapy and chemotherapy.

Van Meir, who joined Emory in 1998, is the director of the Laboratory for Molecular Neuro-Oncology and the co-director of the Emory Winship Cancer Institute Brain Tumor Program. He has devoted his research career to the study of brain tumors, studying the biology and genetics of these cancers and developing new experimental therapies. His laboratory has recently focused on drug discovery with the aim of translating new findings of anti-cancer activity in mouse models to accelerated testing in patients. For more information visit http://neurosurgery.emory.edu/FacultyVanMeir.htm

"It takes a lot of dedication by many talented individuals, and we have been fortunate to have incredible collaborators without which these discoveries would not have been possible," says Van Meir. "Our small molecule work has greatly benefited from collaborations with the laboratories of Kyriacos C. Nicolaou at the Scripps Research Institute in La Jolla, Binghe Wang at Georgia State University, Ruiwen Zhang at the University of Alabama in Birmingham and Mark Goodman at Emory University.

The Brain Tumor Foundation for Children focuses on providing emotional and informational support to families of children with brain tumors, public education and awareness of the disease, and raising funds to support research for a cure and for the improvement in the treatment and the quality of life of those with pediatric brain tumors. http://www.braintumorkids.org

-----------
www.fayettefrontpage.com
Fayette Front Page
News You Can Use
Fayetteville, Peachtree City, Tyrone

Debunking Top Health Myths Even Doctors Believe

(SPM Wire) Do you think that you need eight glasses of water a day, that reading in dim light damages your eyes or that eating turkey makes you sleepy? Think again.

In a study entitled "Medical Myths Even Doctors Believe" published in the "British Medical Journal," Indiana University School of Medicine researchers explored some commonly held and untrue medical beliefs.

The researchers studied various myths -- including those seemingly age-old beliefs that people only use 10 percent of their brains and that hair and fingernails continue to grow after we die.

The surprising findings are that all these beliefs were unproven or untrue.

"We got fired up about this because we knew that physicians accepted these beliefs and were passing this information along to their patients… We didn't set out to become myth busters," said the study's co-author Dr. Aaron Carroll, assistant professor of pediatrics and a Regenstrief Institute, Inc. affiliated scientist.

The first belief they explored was that people should drink at least eight glasses of water a day. This advice has long been promoted as healthful as well as a useful dieting or weight control strategy.

"When we examined this belief, we found that there is no medical evidence to suggest that you need that much water," said Dr. Rachel Vreeman, a pediatrics research fellow and co-author of the new study.

She thinks this myth can be traced back to a 1945 recommendation from the Nutrition Council. But an important part of the Council's recommendation has been lost over the years -- the large amount of fluid contained in food, especially fruits and vegetables, as well as in the coffee and soda people drink each day should be included in the recommended total.

Indeed, drinking excess water can be dangerous, resulting in water intoxication and even death, the study authors note.

Even before Abe Lincoln was told that reading in dim candle light was bad for his eyes, people have believed that reading in dim light causes permanent eye damage. And ever since, generation after generation of parents have thusly admonished children caught reading with flashlights under their blankets.

However, the new study found no evidence that reading in dim light causes permanent eye damage. It is true that eye strain can occur in dim light, causing some temporarily decreased acuity, but after rest the eyes return to their full potential.

And don't worry about falling asleep at the dinner table after gnawing on a turkey drumstick.

Yes, scientific evidence supports that tryptophan, which is contained in turkey, can cause drowsiness. However, turkey doesn't contain an exceptional amount of tryptophan. In fact, turkey, chicken, and ground beef contain about the same amount of tryptophan and protein sources like pork and Swiss cheese contain more tryptophan per gram than turkey.

So why do people believe eating turkey makes them sleepy but never feel that way after a burger or pork chop? This myth most likely gained credence because turkey is often consumed during large, heavy dinners. It's the total content of the meal that makes one feel lethargic.

Dr. Vreeman and Dr. Carroll also explored the popular belief that we use only 10 percent of our brains. MRI scans, PET scans and other imaging studies show no dormant areas of the brain, and even viewing individual neurons or cells reveals no inactive areas of the brain. Metabolic studies of how brain cells process chemicals show no nonfunctioning areas.

This myth probably originated with self improvement experts in the early 1900s who wanted to convince people that they had yet not reached their full potential. With the help of these self proclaimed experts one could tap into the 90 percent of the brain supposedly not being used.

The study also showed that finger nails and hair do not grow after death and that shaved hair does not grow back faster, coarser or darker, among other popularly-held incorrect medical myths.

Army Aims to Better Identify Soldiers with Brain Injuries

By C. Todd Lopez
Special to American Forces Press Service

An Army report released yesterday outlines how the service can better identify and help soldiers who have suffered traumatic brain injuries.

The report contains some 47 recommendations to help the Army better prevent, screen, diagnose, treat and research traumatic brain injury, said Brig. Gen. Donald Bradshaw, who led the task force charged with investigating TBI. Bradshaw is commander of Southeast Regional Medical Command and Eisenhower Regional Medical Center, at Fort Gordon, Ga.

"Our report indicates that, like our civilian counterparts, the Army has done well in the identifying and treatment of severe or penetrating traumatic brain injury, but is challenged to understand, diagnose and treat personnel who have suffered short-term or persistent symptoms of mild TBI," he said. "The task force identified opportunities for improvement as well as best-practice guidelines."

The general said 80 percent of those who suffer from mild TBI, commonly known as a concussion, recover completely. Some 10 to 20 percent of soldiers and Marines returning from Iraq and Afghanistan with experience in combat may have suffered symptoms consistent with mild TBI.

Today, eight of the recommendations made by the task force have already been implemented, said Col. Judith Ruiz, deputy director for rehabilitation and reintegration with the Office of the Surgeon General.

"We have made significant progress to take care of soldiers and to standardize practices across the Army medical department," she said.

Some of the recommendations that have already been implemented include:

-- Working with interagency and civilian groups to better define TBI;

-- Implementing in-theater TBI screening and documentation for all soldiers exposed to brain injury-inducing trauma;

-- Adding TBI-specific questions to deployment-related health assessments;

-- Developing a proposal on the appropriate functions of a "TBI center of excellence";

-- Proposing the Defense and Veterans Brain Injury Center as the core of the new center of excellence;

-- Optimizing the positioning of clinical, educational and research activities;

-- Centralizing the evaluation of the scientific merit, clinical utility, and priority of new treatment strategies, devices or interventions; and

-- Adapting the Military Acute Concussion Evaluation overprint as an approved Department of the Army form to document mild TBI closest to the point of injury.

Ruiz said 31 additional recommendations are in progress, four are planned, and four are in the process of being transferred to other agencies.

For soldiers in theater, the most common cause of brain injury is a blast, such as from an improvised explosive device. But sometimes such blasts do not cause visible external injuries.

"Brain injury does not have to have outside symptoms, such as bleeding," Bradshaw said. "It may, but doesn't have to. That is one of the compounding things; folks may look totally normal, but be dazed."

Because some victims of IEDs or other blasts do not have external injures, they may feel they have not been injured at all -- even if they did sustain a mild TBI.

"It's hard to identify TBI when soldiers don't come forward and don't identify," Bradshaw said. "Some of the actions that have been taken (include) a very big ongoing education process for leaders, soldiers and family members."

The Army launched the post-traumatic stress disorder/mild traumatic brain injury chain teaching program in 2007 to help soldiers better identify signs and symptoms of these conditions and to reinforce the collective responsibility to take care of each other.

The Army is also working to educate the civilian medical community about mild TBI so that soldiers in the reserve components, who may not have full-time access to military medical care, also can be identified, said Col. (Dr.) Jonathan Jaffin, deputy commander of the U.S. Army Medical Research and Material Command.

"One of the things we are concerned with and ... one of the points behind the whole chain teaching was trying to get the message out to the country, not just the active-duty force, Guard and reserve," he said. "(We wanted) the country, including providers throughout the country, to be aware of mild TBI and concussions and the long-term symptoms that some people may be having."

Bradshaw said Army leaders at all levels are committed to the good health and well-being of all soldiers and are proactively addressing the issue of TBI. "Continued research in this area can only help us more clearly understand the medical impacts of the war and the best ways to prevent, recognize and treat soldiers with TBI," he said.

(C. Todd Lopez works for the Army News Service.)